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Titolo:
Acute cytokine response to systemic adenoviral vectors in mice is mediatedby dendritic cells and macrophages
Autore:
Zhang, Y; Chirmule, N; Gao, GP; Qian, R; Croyle, M; Joshi, B; Tazelaar, J; Wilson, JM;
Indirizzi:
Wistar Inst 204, Philadelphia, PA 19104 USA Wistar Inst 204 Philadelphia PA USA 19104 204, Philadelphia, PA 19104 USA Univ Penn, Inst Human Gene Therapy, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 e Therapy, Philadelphia, PA 19104 USA Univ Penn, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA Univ PennPhiladelphia PA USA 19104 ular Engn, Philadelphia, PA 19104 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 3, anno: 2001,
parte:, 1
pagine: 697 - 707
SICI:
1525-0016(200105)3:5<697:ACRTSA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; CYTOTOXIC T-LYMPHOCYTES; GENE-TRANSFER; IN-VIVO; FACTOR-ALPHA; RECOMBINANT ADENOVIRUS; INTERFERON-GAMMA; IL-12 PRODUCTION; INFLAMMATORY RESPONSES; CUTANEOUS INFLAMMATION;
Keywords:
adenovirus; gene therapy; innate immunity; inflammatory cytokines; antigen-presenting cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Wilson, JM Wistar Inst 204, 3601 Spruce St, Philadelphia, PA 19104 USA Wistar Inst 204 3601 Spruce St Philadelphia PA USA 19104 04 USA
Citazione:
Y. Zhang et al., "Acute cytokine response to systemic adenoviral vectors in mice is mediatedby dendritic cells and macrophages", MOL THER, 3(5), 2001, pp. 697-707

Abstract

We investigated the cellular basis for secretion of inflammatory cytokinesin mice following intravenous administration of adenoviral vectors (Ad). Serum inflammatory cytokines including interleukin-6 (IL-6), IL-12, and tumor necrosis factor-alpha (TNF-alpha) were detected as early as 6 h followingintravenous injection of Ad-expressing Escherichia coil P-galactosidase (Ad-lacZ). Ad-lacZ readily accumulated in the splenic marginal zone 1 h afterintravenous infusion, where both dendritic cells (DCs) and macrophages were transduced and activated within 6 h. Flow cytometric analyses showed thatthe expression of ia and CD86 antigens was markedly enhanced on splenic DCs indicating their activation in vivo by Ad-lacZ. Upon ex vivo culture, these early-activated splenic DCs spontaneously produced high levels of IL-6 and IL-12. By contrast, activated splenic macrophages spontaneously secretedonly IL-6. Elimination of tissue macrophages and splenic DCs in vivo considerably reduced the early release of IL-12, IL-6, and TNF-alpha and significantly blocked the specific cellular immune response to Ad and the transgene product in vivo. Our findings indicate that preferential activation of DCs and macrophages may account for Ad-triggered acute inflammatory response in vivo in mice. Moreover, DCs and macrophages may play different roles in this process in terms of their abilities to produce distinct patterns of inflammatory cytokines.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 20:06:09